PROJECT SUMMARY/ABSTRACT This is an R21 proposal for an exploratory research aiming to establish the initial steps toward a novel in vivo mapping technology to transform the clinical study of mechanical and electrical activation waves in the heart. The dynamic mechanical cardiac contraction is two-way coupled to the complex activity associated with dynamic electrical excitations. Disorders in the contraction and excitation dynamical actions, as well as the dissociation in their spatiotemporal coupling, underlie many abnormal conditions, including fatal heart failure and arrhythmias. Our long term goal is to develop a paradigm-shifting approach for studying the highly coupled and dynamic electrical and mechanical activities in the heart in vivo; the central premise of this proposal is that a simultaneous spatiotemporal mapping capable of resolving the mechanical and the electrical activities is critical for understanding mechanisms of health and disease in the heart. Information on the separated dynamical patterns of contraction and excitation waves will enable determining their individual and cooperative role in cardiac disease. Thus, the general objective of this proposal is to demonstrate the feasibility of a new label-free photonics approach for imaging the spatiotemporal patterns of mechanical and electrical associated activities to provide multi-parametric insight into mechanisms of dynamical excitation and contractility. Our developments will be based on movie-format imaging of the heart at short-wave infrared (SWIR; ~1-2.5 m) light range, which has relatively low blood absorbance and scattering, and which has been proposed recently for both deep tissue and in vivo studies. We propose to use here the sheep heart as a platform model to test the general hypothesis that label-free hyperspectral SWIR light imaging will simultaneously characterize the separated dynamical nature of factors associated with electrical and mechanical cardiac activity. The specific aims in this launching project are as follows: Aim 1: To demonstrate the separability between intrinsic hyperspectral SWIR light imaging of cellular electrical and contraction associated activities. Here we will identify wavelengths in the SWIR range whose absorbance level is specific to the action potential or the contraction in the cell. Aim 2: To determine the differential sensitivity of SWIR light imaging to modulations of the cellular action potential by membrane currents regulators. The correlation between the time-course of the hyperspectral light absorbance and the action potential and contraction will enable a physiological interpretation of the imaging. Aim 3: To demonstrate in blood perfused isolated sheep hearts the relationship between surface reflectance of specific SWIR light bands and propagation of electrical and mechanical associated waves. Here we will optimize the new mapping method for future in vivo clinical application. For example, the foreseen new photonic-based approach will be safe and provide real-time and accurate mapping for guidance of ablation to terminate arrhythmias in the clinic. Overall, accomplishment of the aims will lead to an entirely new, label-free imaging modality for in vivo mapping of simultaneous dynamic electrical and mechanical function of the heart.